{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T19:13:56Z","timestamp":1775502836574,"version":"3.50.1"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"am","delay-in-days":18,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>FOXR2 is a forkhead box transcription factor implicated in central nervous system neuroblastoma (CNS-NB FOXR2). The underlying genetic mechanisms and clinical features of CNS-NB FOXR2 have yet to be elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Six CNS-NB FOXR2 cases were identified through DNA methylation profiling. Optical genome mapping, chromosomal microarray, whole genome sequencing, OncoKids panel, RNA-sequencing, and clinical data were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Case 1 demonstrated a 13-kb insertion approximately 25\u2009kb upstream of FOXR2. Case 2 showed two non-contiguous focal gains in Xp11.21 (encompassing FOXR2) and Xp22.2p22.13, approximately 37\u2009Mb apart, resulting from a complex rearrangement disrupting the FOXR2 regulatory region. Case 3 harbored a pericentric inversion between RLIM and a site 17.98\u2009kb upstream of FOXR2. Recurrent copy number alterations included 1q gain (100%), 16q loss (80%), distal 11q loss (60%), and gain of chromosomes 8 and 17q (40% each). All three female patients showed X chromosome loss. FOXR2 expression was elevated in both cases with available RNA-seq data.<\/jats:p>\n                    <jats:p>Overall survival ranged from 1.81-15.62 years. Clinical treatment was highly variable, and molecular testing was unavailable at diagnosis for 4 of 5 patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Structural disruption of the FOXR2 regulatory region, recurrent copy number alterations, and elevated FOXR2 expression are features of CNS-NB FOXR2. These rearrangements do not alter the coding region and may not be detected by routine testing. Initial pathology may suggest other entities, highlighting the importance of molecular testing at diagnosis. Favorable clinical outcomes require accurate initial diagnosis as evidenced by our clinical cohort.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuped\/wuag014","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T18:23:21Z","timestamp":1775499801000},"source":"Crossref","is-referenced-by-count":0,"title":["FOXR2-Activated CNS Neuroblastoma: Characterized by Variable Structural Disruption of the\n                    <i>FOXR2<\/i>\n                    Regulatory Region, Recurrent Copy Number Alterations, and Elevated\n                    <i>FOXR2<\/i>\n                    Expression"],"prefix":"10.1093","author":[{"given":"Jianling","family":"Ji","sequence":"first","affiliation":[{"name":"Children\u2019s Hospital Los Angeles Department of Pathology and Laboratory Medicine, , Los Angeles, CA"},{"name":"Keck School of Medicine of University of Southern CA Department of Pathology, , Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venkata","family":"Yellapantula","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles Department of Pathology and Laboratory Medicine, , Los Angeles, CA"},{"name":"Keck School of Medicine of University of Southern CA Department of Pathology, , Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong","family":"Xu","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles Department of Pathology and Laboratory Medicine, , Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dolores","family":"Estrine","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles Department of Pathology and Laboratory Medicine, , Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Markowitz","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles Department of Pathology and Laboratory Medicine, , Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Han","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles Department of Pathology and Laboratory Medicine, , Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Ma","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles Department of Pathology and Laboratory Medicine, , Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cindy","family":"Fong","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles Department of Pathology and Laboratory Medicine, , Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debra","family":"Hawes","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles Department of Pathology and Laboratory Medicine, , Los Angeles, CA"},{"name":"Keck School of Medicine of University of Southern CA Department of Pathology, , Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley","family":"Margol","sequence":"additional","affiliation":[{"name":"Keck School of Medicine of University of Southern CA Deparmtent of Pediatrics, , Los Angeles, CA"},{"name":"Children\u2019s Hospital Los Angeles Cancer and Blood Disease Institute, , Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrina","family":"O\u2019Halloran","sequence":"additional","affiliation":[{"name":"Keck School of Medicine of University of Southern CA Deparmtent of Pediatrics, , Los Angeles, CA"},{"name":"Children\u2019s Hospital Los Angeles Cancer and Blood Disease Institute, , Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan J","family":"Robison","sequence":"additional","affiliation":[{"name":"Keck School of Medicine of University of Southern CA Deparmtent of Pediatrics, , Los Angeles, CA"},{"name":"Children\u2019s Hospital Los Angeles Cancer and Blood Disease Institute, , Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaclyn A","family":"Biegel","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles Department of Pathology and Laboratory Medicine, , Los Angeles, CA"},{"name":"Keck School of Medicine of University of Southern CA Department of Pathology, , Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer A","family":"Cotter","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles Department of Pathology and Laboratory Medicine, , Los Angeles, CA"},{"name":"Keck School of Medicine of University of Southern CA Department of Pathology, , Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordana","family":"Raca","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles Department of Pathology and Laboratory Medicine, , Los Angeles, CA"},{"name":"Keck School of Medicine of University of Southern CA Department of Pathology, , Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica W","family":"Tsai","sequence":"additional","affiliation":[{"name":"Keck School of Medicine of University of Southern CA Deparmtent of Pediatrics, , Los Angeles, CA"},{"name":"Children\u2019s Hospital Los Angeles Cancer and Blood Disease Institute, , Los Angeles, CA"},{"name":"Children\u2019s Hospital Los Angeles, Saban Research Institute , Los Angeles, CA"},{"name":"USC Norris Comprehensive Cancer Center, Epigenetic Regulation in Cancer Program , Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,3,19]]},"container-title":["Neuro-Oncology Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/neuro-onc-peds\/advance-article-pdf\/doi\/10.1093\/neuped\/wuag014\/67861576\/wuag014.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/neuro-onc-peds\/advance-article-pdf\/doi\/10.1093\/neuped\/wuag014\/67861576\/wuag014.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T18:23:21Z","timestamp":1775499801000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/neuro-onc-peds\/advance-article\/doi\/10.1093\/neuped\/wuag014\/8606820"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,19]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/neuped\/wuag014","relation":{},"ISSN":["2977-4454"],"issn-type":[{"value":"2977-4454","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,19]]},"article-number":"wuag014"}}